3M Drug Delivery Systems MRI Induced RF Heating of Transdermal Patches The following list of FDA approved transdermal patches contain metalized layers in their backing films: Catapres-TTS® (clonidine) Synera® (lidocaine / tetracaine) Habitrol® (nicotine) NicoDerm® CQ® (nicotine) Neupro® (rotigotine) Transderm Scōp® (scopolamine) Androderm® (testosterone) The FDA Advisory also identified Nicotrol® TD (nicotine), Prostep® (nicotine), SALONPAS® Power Plus (methyl salicylate and menthol), Lidopel® (lidocaine and epinephrine), and an unidentified fentanyl patch in their list of transdermal products containing metalized components. While Nicotrol and Prostep patches do contain metalized components, these products have been discontinued in the U.S. We were unable to confirm the metallic content in SALONPAS Power Plus, Lidopel, and the undisclosed fentanyl patch due to lack of product information or availability. To date, only anecdotal effects have been reported regarding specific patients experiencing skin burns while wearing metalized transdermal patches during MRI procedures. No skin burns have been reported by patients wearing nonmetalized transdermal patches during MRI procedures. There have been no studies to explore the MRI induced RF heating effect in metalized transdermal patches. We evaluated the MRI induced RF heating in transdermal patches and component films by using an experimental system which consisted of the magnetic resonance (MR) test system, a phantom gel, temperature sensors, and the test film. We used marketed transdermal patches and commercially available backing films to quantify the temperature increase associated with RF power deposition, and identified factors that influence the degree of temperature increase. These data can be used to understand the MRI safety of transdermal patches. A phantom saline gel was used to simulate the electrical and thermal properties of human tissue at 64 MHz. The gel consisted of 1.32 g/L NaCl (Sigma Aldrich) and 10 g/L polyacrylic acid (Sigma Aldrich) in distilled water. A Lexan container was filled with approximately 25 kg of this tissue-mimicking gelled saline. The container was constructed such that a torso gel phantom could be prepared of dimensions recommended by ASTM F2182-09 to appropriately load the coil and measure heating. Scotchpak 1109 Scotchpak 9723 The test films consisted of metalized and nonmetalized backing films (all from 3M Drug Delivery Systems): ScotchpakTM 1109 – 1.3 mil tan pigmented PE/metalized PET laminate film ScotchpakTM 9723 – 1.7 mil tan pigmented PE/PET laminate film (nonmetalized) ScotchpakTM 9735 - 2 mil PE/PET laminate film (nonmetalized) CoTranTM 9720 – 3 mil PE film (nonmetalized) ScotchpakTM HB-T 19733 - 2 mil EVA/AlOx PET laminate film (nonmetalized) Commercially available transdermal patches evaluated in this study included Habitrol® (Novartis Consumer Health), NicoDerm® CQ® (GlaxoSmithKline), Catapres-TTS® (Boehringer Ingelheim), and Transderm Scōp® (Novartis Consumer Health). NicoDerm CQ was tested in opaque (metalized) and clear (nonmetalized) versions. Experimental Method – Procedure The backing films were evaluated in circular (2.5 and 40 cm2) and rectangular (40 cm2) shapes. Two rectangular dimensions were evaluated – short (7.2 cm x 5.6 cm) and long (15.2 cm x 2.6 cm). The transdermal patches were tested in their original converted shapes and sizes. Locations and orientations of the test materials on the phantom gel were chosen according to usage and ASTM F2182-09 recommendations. Each material was placed close to the body coil, since this placement was expected to induce maximum current and maximum heating. Each material was placed horizontally on the gel surface to mimic real-life application. Fluoroptic® Temperatures were measured using RF-transparent temperature probes (Lumasense Technologies, Luxtron 3000). Temperature probes were taped to each test material to determine maximum heating. Temperature was measured as a function of time at the test material and a reference location on the phantom gel. RF power was deposited for 15 minutes at the measured whole body average SAR of 4 W/kg from the generic body coil. 2.5 cm2 circle 40 cm2 circle 40 cm2 short rectangle 40 cm2 long rectangle 1.6 (1.5) 4.1 (1.5) 4.0 (0.8) 10.5 (1.7) No 40 cm2 circle 40 cm2 long rectangle 1.5 (1.3) 1.5 (0.8) Scotchpak 9735 No 40 cm2 long rectangle 1.5 (1.0) CoTran 9720 No 40 cm2 long rectangle 2.0 (1.4) Scotchpak HB-T 19733 No 40 cm2 long rectangle 1.3 (0.9) Transdermal Patch Yes Metalized Configuration Tested dTmax (ºC) Catapres TTS Yes 3.5 cm2 square (0.1 mg) 10.5 cm2 square (0.3 mg) 1.6 (1.5) 1.7 (1.3) Habitrol Yes 10 cm2 circle (7 mg) 30 cm2 circle (21 mg) 2.0 (1.2) 2.7 (1.3) Nicoderm CQ (Opaque) Yes 22 cm2 rectangle (21 mg) 2.3 (1.1) Nicoderm CQ (Clear) No 22 cm2 rectangle (21 mg) 1.9 (1.1) Transderm Scōp Yes 2.5 cm2 circle (1.5 mg) 1.8 (1.0) Scotchpak 1109 – 2.5 cm2 circle 21 20 19 18 17 16 15 Reference East Edge North Edge West Edge 0 5 10 15 20 25 30 35 Time (minutes) Scotchpak 1109 – 40 cm2 circle 18 16 Reference North Edge West Edge South Edge 14 12 10 0 5 10 15 20 25 Time (minutes) The plots above show results from two different configurations for circular Scotchpak 1109 films. For each, the temperature rises coincided with the start of RF power deposition. The discontinuation of RF power deposition coincided with constant or decrease in temperature. The temperature rise for the small film was equivalent to that for the gel reference location. Here, the effect can be attributed solely to heating of the gel. Similar temperature profiles were observed with the nonmetallic films. The large film showed significantly more heating. Here, the effect can be attributed to ohmic heating of the film. Temperature (ºC) The MR test system was a generic 1.5 T (64 MHz) shielded birdcage body coil. A total RF power of 100 W was delivered to the coil to simulate the FDA guideline maximum allowable whole-body-average specific absorption rate (SAR) of 4 W/kg. Time durations and SARs used to produce RF heating were in accordance with the recommendations of ASTM F2182-09 and MR-safety guidelines. Scotchpak 1109 – 40 cm2 short rectangle Scotchpak 1109 – 40 cm2 long rectangle Reference End 1 End 2 Center Edge 22 21 20 19 18 17 16 15 0 5 Reference End 1 End 2 Center Edge 30 28 26 24 22 20 18 16 14 0 10 15 20 25 30 35 5 10 15 20 25 30 35 Time (minutes) Time (minutes) The two plots above show how shape influences the ohmic heating response in rectangular Scotchpak 1109 films. The short rectangular film (nearly square) heated equivalently at all edges. The long rectangular film heated significantly more at its two ends compared to its center, which showed heating no different than the gel reference. Habitrol – 10 cm2 (7 mg) circular patch Habitrol – 30 cm2 (21 mg) circular patch Temperature (ºC) It has been proposed that the skin burns are due to heating of the metal component in the patch, which is typically a thin layer of nonferromagnetic vapor coated aluminum in the backing film of the patch. The electromagnetic field used to create the magnetic resonance signal induces an electric current in the conductive metalized layer of the patch. The electric currents may cause ohmic heating enough to damage to the skin beneath the transdermal patch. Results and Discussion, continued Results in the table below show the maximum temperature increase (dTmax) beneath each film and patch associated with RF power deposition from the MR test system. dTmax is the difference between the maximum temperature (after 15 minutes of RF power deposition) and the initial temperature when RF power deposition started. The dTmax for the gel reference location is also provided in parentheses. Backing Film Metalized Configuration Tested dTmax (ºC) Temperature (ºC) On March 5, 2009, the FDA issued a Public Health Advisory that warned of the risk of skin burns during MRI scans from transdermal patches with metallic backings. The Advisory identified several transdermal patch products in the U.S. that contain metal components. Results and Discussion Experimental Method – MR Test System Temperature (ºC) Introduction Temperature (ºC) Drug Delivery Systems, St. Paul, MN R. Gordon1, R. Visaria2, D. Shrivastava3, and J. Thomas Vaughan3 2MR Safe Devices, Burnsville, MN 3Center for Magnetic Research, University of Minnesota, Minneapolis, MN Temperature (ºC) 13M Reference Edge 1 Edge 2 Edge 3 Center 22 21 20 19 18 17 16 0 5 10 15 20 25 18 17 Reference Edge 1 Edge 2 Edge 3 16 15 14 0 5 10 15 20 25 30 35 40 Time (minutes) Time (minutes) Significant ohmic heating was observed only for 2 of 6 patches. For these two patches, 30 cm2 Habitrol and 22 cm2 Nicoderm CQ, the temperature rises were 1ºC more than the temperature rises in the respective gel reference locations. Two representative plots are shown above. For the 10 cm2 Habitrol patch, the temperature rises at the patch edges were slightly greater than the reference. The temperature rise in the center of the patch was equivalent to that of the reference, which again suggests that location influences the degree of ohmic heating. For the 30 cm2 Habitrol patch, the temperature increased significantly more at each edge location compared to the 10 cm2 Habitrol patch. Conclusion MRI induced ohmic heating occurred only in metalized backing films. The heating was attributed solely to the metalized layer in the films. In addition, the results show that the degree of ohmic heating was a function of the size and shape of the film and location on the film. The greatest heating occurred at the edge of 40 cm2 films, particularly at the edge of large, rectangular films. For transdermal patches, ohmic heating was negligible for patches less than 10 cm2 in size. Significant ohmic heating occurred only in the 30 cm2 Habitrol patch and the 22 cm2 Nicoderm CQ patch.
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